Waist circumference outperforms cardiometabolic indices for identifying hypogonadism in Klinefelter Syndrome

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ID: 332317
2026
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Abstract
Abstract Context Klinefelter syndrome (KS) is characterized by primary hypogonadism and increased cardiometabolic risk. The utility of cardiometabolic indices remains unclear. Objective To evaluate whether anthropometric and cardiometabolic indices provide incremental value beyond age for identifying hypogonadism in men with KS. Design and Setting Retrospective cross-sectional cohort study at a tertiary referral center. Patients 580 patients with KS were evaluated. Analyses assessing biochemical hypogonadism were restricted to untreated patients with available calculated free testosterone (cFT) concentrations (n = 328). Main outcome measures Biochemical androgen deficiency was defined as cFT <0.220 nmol/L. Discriminative performance and incremental value of WC, LAP, TyG, and HOMA-IR were assessed using logistic regression, ROC analyses, reclassification analyses, decision curve analysis (DCA), and bootstrap validation. Results Among untreated patients, 64.9% had biochemical hypogonadism. WC showed the highest discriminative ability (AUC 0.747) and slightly greater discrimination than cardiometabolic indices including LAP (AUC 0.704), HOMA-IR (AUC 0.681), and TyG index (AUC 0.612). In multivariable analyses adjusted for age, WC remained independently associated with hypogonadism (OR 1.05 per cm; p < 0.001). Age alone yielded an AUC of 0.744, which increased to 0.796 after addition of WC (p = 0.007), whereas addition of LAP resulted in only modest improvement (AUC 0.758). Addition of WC improved reclassification beyond age. DCA demonstrated consistent gains in clinical net benefit with inclusion of WC, whereas composite cardiometabolic indices provided limited additional utility. Conclusions In KS, WC provides incremental value beyond age for identifying hypogonadism, whereas composite cardiometabolic indices offer limited additional discriminatory value. These findings suggest that simple anthropometric assessment may support endocrine-metabolic stratification in KS.
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Authors Andrea Graziani, Matteo Nardin, Giuseppe Grande, Riccardo Maria Pollis, Andrea Delbarba, Antonella Di Mambro, Riccardo Selice, Carlo Cappelli, Gian Paolo Fadini, Alberto Ferlin
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Journal the journal of clinical endocrinology & metabolism
Year 2026
DOI
10.1210/clinem/dgag426
URL
https://doi.org/10.1210/clinem/dgag426
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